The goal of this randomized clinical trial is to compare autologous platelet-rich plasma (PRP) with gonadotropin for improving ovarian response in women with letrozole-resistant polycystic ovary syndrome (PCOS). Researchers will compare the two treatments to assess ovarian response, ovulation rates, and pregnancy rates. Participants will be randomly assigned to receive either intra-ovarian autologous PRP or gonadotropin treatment and will be followed for three consecutive cycles.
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that may cause anovulation and infertility. Letrozole is a first-line ovulation induction agent; however, a proportion of women with PCOS are resistant to standard-dose letrozole and may require second-line treatment such as gonadotropin therapy. Gonadotropin treatment can be effective but requires monitoring because of the risks of ovarian hyperstimulation and multiple pregnancy. This randomized clinical trial is designed to evaluate and compare the effects of intra-ovarian autologous platelet-rich plasma (PRP) and gonadotropin treatment on ovarian response in women with letrozole-resistant PCOS. Eligible women attending the Department of Reproductive Endocrinology and Infertility, Bangladesh Medical University, will be identified according to the Rotterdam diagnostic criteria for PCOS and screened according to the study inclusion and exclusion criteria. Participants will receive detailed information about the study and provide written informed consent before enrollment. Sociodemographic information, relevant clinical history, and investigations will be recorded using a structured data collection sheet. Participants will be randomly allocated into two intervention groups using a computer-generated random number sequence. Participants in the experimental group will receive 5 mL of autologous platelet-rich plasma in each ovary by laparoscopy during the proliferative phase of the menstrual cycle. Following the procedure, participants will be monitored for spontaneous ovulation for three consecutive months. Participants in the gonadotropin group will receive gonadotropin stimulation for three consecutive cycles. Follicular development will be monitored by transvaginal ultrasonography. Gonadotropin stimulation will be administered according to the study protocol, followed by human chorionic gonadotropin triggering when a mature follicle is identified. Timed intercourse will be advised following triggering. Ovulation will subsequently be assessed by mid-luteal serum progesterone measurement. Tubal patency will be assessed as part of the infertility evaluation to exclude tubal factor infertility. In participants allocated to the PRP group, tubal evaluation will be performed during the laparoscopic procedure undertaken for intra-ovarian PRP administration. In participants allocated to the gonadotropin group, tubal evaluation will be performed before initiation of gonadotropin stimulation. Participants found to have bilateral tubal block will be excluded from the study. The primary outcome is ovarian response, assessed by transvaginal ultrasonography, including the proportion of participants developing follicles measuring at least 14 mm, the proportion developing mature follicles measuring 18-25 mm, and endometrial thickness of at least 7 mm. Ovulation rate will be assessed by mid-luteal serum progesterone, with a progesterone concentration greater than 3 ng/mL considered indicative of ovulation. Pregnancy rate will be assessed by serum beta-human chorionic gonadotropin. Participants will also be monitored for treatment-related adverse effects, including ovarian hyperstimulation syndrome, multiple pregnancy, and injection-site reactions. The study will compare ovarian response, ovulation rate, and pregnancy rate between the intra-ovarian autologous PRP group and the gonadotropin group over three consecutive treatment cycles/months. The study aims to determine whether intra-ovarian autologous PRP may improve ovarian response and ovulation in women with letrozole-resistant PCOS compared with gonadotropin treatment.
Participants will receive 5 mL of autologous platelet-rich plasma (PRP) in each ovary by laparoscopy during the proliferative phase of the menstrual cycle. Following the procedure, participants will be monitored for spontaneous ovulation for three consecutive cycles.
Participants will receive recombinant follicle-stimulating hormone (rFSH) 75 IU intramuscularly on days 5 and 7 of the menstrual cycle, followed by human menopausal gonadotropin (hMG) 75 IU intramuscularly on days 9 and 11. Follicular development will be monitored by transvaginal ultrasonography. When at least one mature follicle measuring 18-25 mm is identified, ovulation will be triggered with human chorionic gonadotropin (hCG) 5,000 IU intramuscularly, followed by timed intercourse.
Department of Reproductive Endocrinology and Infertility, Bangladesh Medical University
Dhaka, Dhaka Division, Bangladesh
Proportion of Participants With Developing Follicles ≥14 mm
Developing follicles will be assessed by transvaginal ultrasonography. A follicle measuring ≥14 mm in diameter will be considered a developing follicle.
Time frame: Day 12 to Day 14 of each treatment cycle, where each treatment cycle is defined as one menstrual cycle from the first day of menstrual bleeding to the first day of the next menstrual bleeding, for up to three consecutive treatment cycles.
Proportion of Participants With Mature Follicles
Mature follicle will be defined as a follicle measuring 18 to 25 mm in diameter on transvaginal ultrasonography.
Time frame: Day 12 to Day 14 of each treatment cycle, where each treatment cycle is defined as one menstrual cycle from the first day of menstrual bleeding to the first day of the next menstrual bleeding, for up to three consecutive treatment cycles.
Proportion of Participants With Endometrial Thickness ≥7 mm
Endometrial thickness will be measured by transvaginal ultrasonography. An endometrial thickness of ≥7 mm will be considered the target response
Time frame: Day 12 to Day 14 of each treatment cycle, where each treatment cycle is defined as one menstrual cycle from the first day of menstrual bleeding to the first day of the next menstrual bleeding, for up to three consecutive treatment cycles.
Proportion of Participants With Ovulation
Ovulation will be assessed by mid-luteal serum progesterone measurement. A serum progesterone level \>3 ng/mL will be considered indicative of ovulation
Time frame: 7 days after ovulation trigger in each treatment cycle, where each treatment cycle is defined as one menstrual cycle from the first day of menstrual bleeding to the first day of the next menstrual bleeding, for up to three consecutive treatment cycles.
Pregnancy Rate
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Pregnancy will be assessed by quantitative serum beta-human chorionic gonadotropin (β-hCG) measurement one week after a missed menstrual period. Clinical pregnancy will be confirmed by transvaginal ultrasonography at 6-8 weeks of gestation
Time frame: One week after a missed menstrual period in each treatment cycle, where each treatment cycle is defined as one menstrual cycle from the first day of menstrual bleeding to the first day of the next menstrual bleeding, for up to three consecutive treatment